CFS

A new retrovirus, xenotropic murine leukaemia virus-related virus (XMRV), first identified in tumor tissue of individuals with prostate cancer, was subsequently found in 68 of 101 US patients with chronic fatigue syndrome (CFS). This observation raised the possibility that XMRV is the etiologic agent of CFS. An important question is whether XMRV is associated with CFS in other parts of the world. For some CFS patients in the UK the answer appears to be no.

The subjects of this study were 186 confirmed CFS patients who had been referred to the CFS clinic at King’s College Hospital, London. DNA was prepared from blood samples and subjected to polymerase chain reaction using primers that anneal to an XMRV-specific sequence, and to a sequence conserved among murine leukemia viruses. To demonstrate that the amplification worked, a positive control reaction was done using XMRV DNA. The reaction products were fractionated by electrophoresis on an agarose gel, and the DNAs were visualized by staining with a dye. As shown in the figure, positive control samples containing XMRV DNA produced DNAs of the expected sizes (lanes 10, 11). None of the 186 test DNAs from CFS patients produced a PCR product with either the XMRV or murine leukemia virus primers. Some of these negative samples are shown in lanes 1-8 of the figure.

The authors of this study suggest that they were more careful at avoiding contamination than the group which previously identified XMRV in American CFS patients:

…the PCR operator was blinded to the provenance of the DNA samples. In fact, with the exception of the PCR controls, all 186 DNA test samples originated from CFS patients. Care was taken to grow the XMRV plasmid in a laboratory in which no MLV had been cultured and no MLV vectors used and the PCR was carried out in a CPA-accredited Molecular Diagnostics Unit which processes only human tissue. Multiple (six) water (negative) controls were included in every run to detect low level contamination and a PCR to amplify a sequence that is conserved in most murine leukaemia viruses was included in order to expose any circulating MLV contamination and to detect any variant of XMRV that might be circulating in the UK CFS population.

But they also acknowledge that there might be population differences in XMRV distribution:

Based on our molecular data, we do not share the conviction that XMRV may be a contributory factor in the pathogenesis of CFS, at least in the U.K.

These results are surely a disappointment to CFS sufferers who believe that XMRV is the etiologic agent of the disease. But they reveal the dangers of making conclusions about disease etiology based on the findings of limited studies. As I wrote previously, while the presence of XMRV in 67% of CFS samples seems impressive, it could be misleading. For example, the samples could be from regions where XMRV infection is common.

In light of these new findings, it is informative to recall that the nucleic acid of another retrovirus, human T-lymphotropic virus type ll, was previously amplified from blood cells of 23 of 30 CFS patients, but not from healthy patients. However this observation was not confirmed in subsequent studies of CFS patients. In addition, there is no evidence for the presence of other retroviruses in CFS patients, including HIV-1, bovine and feline leukemia viruses, simian T lymphotropic virus type l, foamy virus, and simian retrovirus.

It is possible that XMRV is involved in CFS but only in certain parts of the world. More extensive studies such as the one reported here must be done worldwide to clarify the role of XMRV in CFS, and to determine whether other infectious agents are involved.

Erlwein O, Kaye S, McClure MO, Weber J, Wills G, Collier D, Wessely S, & Cleare A (2010). Failure to detect the novel retrovirus XMRV in chronic fatigue syndrome. PloS one, 5 (1) PMID: 20066031